John Rothwell – Abstract

Brain stimulation and treatment of motor impairments

Rothwell, J
UCL Queen Square Institute of Neurology, London UK

There is good evidence in animal models that following stroke there is a general up-regulation of synaptic plasticity in the surviving tissue that occurs at the same time as a rapid improvement in behavioural outcome. Genes important for growth, repair and plasticity are activated rapidly following infarct as well as expression of growth stimulating genes in the first week following ischaemic infarct which is then followed by up-regulation of growth inhibiting genes. Circulating levels of molecules that support developmental critical period neuroplasticity are also up-regulated following focal infarcts in animal models. Together these findings suggest a period of increased capacity for reorganisation following stroke and that there may be a window of enhanced neuroplastic potential in the weeks after injury.

I will describe an investigation in which we used theta burst TMS to probe the amount of plasticity in a group of 30 patients from 2 weeks to 6 months after a unihemispheric stroke affecting upper limb function. We opted to investigate the plasticity in the non-stroke hemisphere for the practical reason that following stroke it is sometimes not possible to evoke any muscle twitches with TMS of the affected hemisphere. By using the non-stroke hemisphere we could ensure that we would be able to study all patients. In addition, the animal data show that the post-stroke changes in plasticity are not confined to the damaged areas of brain, but are seen widely even in the non-stroke hemisphere. We found that there was an enhanced response to the plasticity protocol early after stroke which then receded by 6 months. Although we have no measures of an individual’s pre-stroke plasticity, the data would be consistent with the notion that in human patients, as in animals, there is a short “window” of increased synaptic plasticity in the motor system that might contribute to functional recovery. If correct this may be the time when therapy will have the greatest impact.